Resistant Gonorrhoea Research Articles

Oxydifficidin, a potent Neisseria gonorrhoeae antibiotic due to DedA-assisted uptake and ribosomal protein RplL sensitivity

Gonorrhea, which is caused by Neisseria gonorrhoeae, is the second most reported sexually transmitted infection worldwide. The increasing appearance of isolates that are resistant to approved therapeutics raises the concern that gonorrhea may become untreatable. Here, we serendipitously identified oxydifficidin as a potent N. gonorrhoeae antibiotic through the observation of a Bacillus amyloliquefaciens contaminant in a lawn of N. gonorrhoeae. Oxydifficidin is active against both wild-type and multidrug-resistant N. gonorrhoeae. Its potent activity results from a combination of DedA-assisted uptake into the cytoplasm and the presence of an oxydifficidin-sensitive ribosomal protein L7/L12 (RplL). Our data indicate that oxydifficidin binds to the ribosome at a site that is distinct from other antibiotics and that L7/L12 is uniquely associated with its mode of action. This study opens a potential new avenue for addressing antibiotic resistant gonorrhea and underscores the possibility of identifying overlooked natural products from cultured bacteria, particularly those with activity against previously understudied pathogens.

Sustained Effectiveness of Doxycycline Post-Exposure-Prophylaxis in a Large Sexual Health Clinic over 96 Weeks: An Interrupted Time Series Analysis.

Doxycycline post-exposure prophylaxis (doxy-PEP) reduced bacterial sexually transmitted infection (STI) incidence in a sexual health clinic over 96 weeks (n=4,592; 2,524 on doxy-PEP), particularly for chlamydia and syphilis, with smaller effects for gonorrhea. Continued surveillance for gonorrhea and antibiotic resistance is essential to evaluate doxy-PEP's long-term effectiveness.

Acceptability of the gonorrhoea human challenge model to accelerate vaccine development in UK men.

Acceptability of the gonorrhoea human challenge model to accelerate vaccine development in UK men.

Molecular epidemiology of Neisseria gonorrhoeae isolates in Russia, 2015–2023: current trends and forecasting

IntroductionThe emergence of multidrug resistance in N. gonorrhoeae is a serious global problem, and gonorrhea may soon become an incurable disease. The aim of the study was to characterize the N. gonorrhoeae population in Russia from 2015 to 2023 and predict the potential spread of the most concerning clones.MethodsA total of 996 N. gonorrhoeae isolates were examined during the analyzed period. Ceftriaxone and azithromycin susceptibility testing were performed using the agar dilution method. Microarray-based assays and sequencing were employed to identify the genotypes and genetic markers of antimicrobial resistance.ResultsNo ceftriaxone-resistant isolates were found in Russia, however, the number of isolates with reduced susceptibility to ceftriaxone has increased to 22.6% in recent years. Since 2020, approximately 12.5% of isolates have exhibited resistance to azithromycin annually. Two clusters of isolates pose a particular threat to Russia: NG-MAST G2212, linked to MLST 1901/1902, carries a mosaic structure in the penA gene; G12302, linked to MLST 9363, contains mosaic alleles in the mtrR and mtrD genes. Additionally, two new high-risk genogroups were characterized: G18898 and G16206. Both are associated with MLST 10314 and harbor mosaic variants of penA or mtrR/mtrD. Analysis of time series data suggests that isolates with mosaic alleles are unlikely to be eradicated from the population in the near future, potentially worsening the epidemiological situation of gonorrhea in Russia.ConclusionsThe native genetic strains of N. gonorrhoeae in Russia, which are susceptible to cephalosporins and macrolides, are being progressively replaced by globally dominant lineages. To further characterize this epidemiologic shift, ongoing surveillance strategies using molecular epidemiology and the identification of genetic markers will be crucial in curbing the growth and spread of N. gonorrhoeae resistance. Such efforts are vital in ensuring the availability of effective treatments for gonococcal infection.

Dermatology. Doxy PEP and topical JAK inhibitors in inflammatory diseases

This article focuses on two key innovations in dermatology: post-exposure prophylaxis for sexually transmitted infections (STIs) and new therapeutic options for inflammatory skin diseases. New European and American guidelines for doxycycline post-exposure prophylaxis (Doxy PEP) aim to prevent STIs in men who have sex with men (MSM) and individuals on HIV pre-exposure prophylaxis (PrEP). Doxy PEP is effective against syphilis and chlamydia, but its efficacy is limited by growing gonorrhea resistance. At the same time, significant progress has been made in the treatment of certain inflammatory skin diseases. Topical Janus kinase (JAK) inhibitors provide new treatment options for inflammatory skin diseases such as vitiligo and atopic dermatitis by blocking the JAK-STAT pathway. These molecules show a favorable safety profile in topical use, reducing systemic side effects.

Whole-genome sequencing resolves biochemical misidentification of Neisseria species from urogenital specimens.

Neisseria meningitidis (Nm) and Neisseria gonorrhoeae (Ng) are human pathogens that sometimes occupy the same anatomical niche. Ng, the causative agent of gonorrhea, infects 87 million individuals annually worldwide and is an urgent threat due to increasing drug resistance. Ng is a pathogen of the urogenital tract and may infect the oropharyngeal or rectal site, often asymptomatically. Conversely, Nm is an opportunistic pathogen. While often a commensal in the oropharyngeal tract, it is also the leading cause of bacterial meningitis with 1.2 million cases globally, causing significant morbidity and mortality. Horizontal gene transfer (HGT) is likely to occur between Ng and Nm due to their shared anatomical niches and genetic similarity, which poses challenges for accurate detection and treatment. Routine surveillance through the Gonococcal Isolate Surveillance Project and Strengthening the U.S. Response to Resistant Gonorrhea detected six concerning urogenital Neisseria isolates with contradicting species identification in Milwaukee (MIL). While all six isolates were positive for Ng using nucleic acid amplification testing (NAAT) and matrix-assisted laser desorption/ionization time of flight identified the isolates as Ng, two biochemical tests, Gonochek-II and API NH, classified them as Nm. To address this discrepancy, we performed whole-genome sequencing (WGS) using Illumina MiSeq on all isolates and employed various bioinformatics tools. Species detection analysis using BMScan, which uses WGS data, identified all isolates as Ng. Furthermore, Kraken revealed over 98% of WGS reads mapped to the Ng genome and <1% to Nm. Recombination analysis identified putative HGT in all MIL isolates within the γ-glutamyl transpeptidase (ggt) gene, a key component in the biochemical tests used to differentiate between Nm and Ng. Further analysis identified Nm as the source of HGT event. Specifically, the active Nm ggt gene replaced the Ng pseudogenes, ggt1 and ggt2. Together, this study demonstrates that closely related Neisseria species sharing a niche underwent HGT, which led to the misidentification of species following biochemical testing. Importantly, NAAT accurately detected Ng. The misidentification highlights the importance of using WGS to continually evaluate diagnostic or bacterial identification tests.

Effects of doxycycline post-exposure prophylaxis for prevention of sexually transmitted infections on gonorrhoea prevalence and antimicrobial resistance among men who have sex with men in the USA: a modelling study

Doxycycline post-exposure prophylaxis (PEP) has been shown to be efficacious for the prevention of bacterial sexually transmitted infections, but resistance implications for Neisseria gonorrhoeae remain unknown. We aimed to use a mathematical model to investigate the anticipated impact of doxycycline PEP on the burden of gonorrhoea and antimicrobial resistance dynamics in men who have sex with men (MSM) in the USA. Using a deterministic compartmental model, characterising gonorrhoea transmission in a US MSM population comprising three sexual activity groups defined by annual partner turnover rates, we introduced doxycycline PEP at various uptake levels (10-90%) among those with high sexual activity. Infections were stratified by symptom status and resistance profile (ie, susceptible, ceftriaxone-resistant, tetracycline-resistant, or dual-resistant), with ceftriaxone the treatment for active infection. As resistance to tetracycline, not doxycycline, is monitored and reported nationally, we used this as a proxy for doxycycline PEP resistance. We compared the 20-year prevalence, incidence rates, and cumulative incidence of gonococcal infection, resistance dynamics (time to 5% prevalence of ceftriaxone resistance, 5% prevalence of dual resistance, and 84% prevalence of tetracycline resistance), and antibiotic consumption with baseline (ie, no doxycycline PEP). Uptake of doxycycline PEP resulted in substantial reductions in the prevalence and incidence of gonorrhoea, but accelerated the spread of tetracycline resistance. The maximum reduction in prevalence over 20years compared with no uptake ranged from 40·3% (IQR 15·3-83·4) with 10% doxycycline PEP uptake to 77·4% (68·4-84·9) with 90%uptake. Similarly, the maximum reduction in the incidence rate ranged from 38·6% (14·1-83·6) with 10% uptake to 77·6% (68·1-84·7) with 90% uptake. Cumulative gonococcal infections were reduced by a median of 14·5% (IQR8·4-21·6) with 10% uptake and up to 46·2% (26·5-59·9) with 90% uptake after 5years, and by 6·5% (3·4-13·0) with 10% uptake and 8·7% (4·3-36·2) with 90% uptake by 20years. In almost all scenarios explored, doxycycline PEP lost clinical effectiveness (defined as 84% prevalence of tetracycline resistance) within the 20-year period, but itslifespan ranged from a median of 12·1years (IQR 9·9-15·7) with 10% uptake to 1·6years (1·3-1·9) with 90%uptake. Doxycycline PEP implementation had minimal impact on extending the clinical lifespan of ceftriaxone monotherapy (5·0years [IQR 4·0-6·2]), with the median time to 5% prevalence of resistance ranging from 4·8years (3·9-6·0) for 90% uptake to 5·0years (4·1-6·2) for 10% uptake. Similarly, the median time to 5%prevalence of dual resistance to ceftriaxone and tetracycline ranged from 4·8years (3·9-6·0) for 90% uptake to 5·8years (4·8-7·4) for 10% uptake. Median decrease in ceftriaxone consumption for high doxycycline PEP uptake levels compared with baseline ranged from 41·7% (27·0-54·3) for 50% uptake to 50·2% (29·3-62·7) for 90% uptake at 5years, but dropped to 11·8% (6·9-32·0) for 50% uptake and 12·1% (7·0-41·6) for 90% uptake after 20years. Notwithstanding the clear benefits of doxycycline PEP for other sexually transmitted infections, for Ngonorrhoeae, model findings suggest that doxycycline PEP is an effective but impermanent solution for reducing infection burden, given eventual selection for resistant strains. This finding presents a challenge for policy makers considering strategies for doxycycline PEP implementation and oversight: the need to balance the clear, short-term clinical benefits with the risk of harm via antimicrobial resistance. US Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases.

A-296 Streck Urine Preserve Provides Sample Stability for Cepheid Xpert CT/NG test

Abstract Background Sexually transmitted infections (STIs) are one of the most common communicable diseases worldwide and are associated with significant morbidity and mortality. Data indicates that the four curable STIs - chlamydia, gonorrhea, trichomoniasis, and syphilis - cause over 375 million infections annually. Further, the infection rate for gonorrhea has increased by 63% in the United States and the emergence of resistant gonorrhea is an urgent global public health concern. To prevent transmission of gonorrhea and other curable STIs and minimize the escalation of untreated infections, early and effective prevention and control strategies are paramount. Rapid diagnostic testing and nucleic acid amplification tests (NAATs) have become the gold standard for STI detection. However, limited global access to these technologies often requires that samples be shipped to central laboratories for analysis. Current protocols recommend that neat urine be analyzed within 24 hours of collection if stored at 2 °C to 8 °C or within four days if frozen, as prolonged storage and exposure to freeze-thaws can induce cell lysis and release of nucleases, leading to degradation of DNA and false negative test results. Without sample stabilization, laboratories are left with a small window for accurate analysis. Here, we demonstrate that Streck Urine Preserve (SUP) maintains target and donor DNA concentrations during prolonged storage and that these stabilized samples are compatible with Cepheid’s automated GeneXpert System and associated Xpert CT/NG test. Methods Fresh human urine, with or without SUP, was tested neat or spiked with Neisseria gonorrhoeae (N. gonorrhoeae). Samples were stored at room temperature for up to 18 days before being analyzed on the Cepheid GeneXpert System using the Xpert CT/NG test per manufacturer’s instructions. Differences in average Ct values were compared for the sample processing control, sample adequacy control, and N. gonorrhoeae targets. DNA stability was assessed by comparing the changes between fresh and SUP-treated samples throughout the study period. Results Following prolonged storage, Ct values for neat, untreated urine increased by 3-7 cycles, correlating to a 10- to 100-fold decrease in detectable copies of N. gonorrhoeae and the sample adequacy control compared to urine samples stabilized with SUP. The average Ct value for samples stabilized with SUP did not change by more than 1.5 cycles throughout the study period. Additionally, Ct values for the sample processing control remained constant throughout the testing period, indicating that SUP did not impact sample processing. Conclusions When limited point-of-care testing options require storage and shipping of samples to central laboratories, urine stabilizers are imperative to obtain results representative of the patient sample at the time of collection. SUP effectively stabilized N. gonorrhoeae DNA and donor DNA prior to analysis with the Cepheid Xpert CT/NG test. This contrasts with the marked decrease in DNA copy number in non-stabilized urine over the study duration, which may lead to false negative results for low-positive urine samples. Taken together, SUP provides clinical researchers and assay developers with added flexibility when handling, shipping, and processing urine specimens and supports compatibility with automated NAAT systems and tests.

Oxydifficidin, a potent Neisseria gonorrhoeae antibiotic due to DedA assisted uptake and ribosomal protein RplL sensitivity

Gonorrhea, which is caused by Neisseria gonorrhoeae, is the second most reported sexually transmitted infection worldwide. The increasing appearance of isolates that are resistant to approved therapeutics raises the concern that gonorrhea may become untreatable. Here, we serendipitously identified oxydifficidin as a potent N. gonorrhoeae antibiotic through the observation of a Bacillus amyloliquefaciens contaminant in a lawn of N. gonorrhoeae. Oxydifficidin is active against both wild-type and multidrug-resistant N. gonorrhoeae. It’s potent activity results from a combination of DedA-assisted uptake into the cytoplasm and the presence of an oxydifficidin-sensitive ribosomal protein L7/L12 (RplL). Our data indicates that oxydifficidin binds to the ribosome at a site that is distinct from other antibiotics and that L7/L12 is uniquely associated with its mode of action. This study opens a potential new avenue for addressing antibiotic resistant gonorrhea and underscores the possibility of identifying overlooked natural products from cultured bacteria, particularly those with activity against previously understudied pathogens.

Providing adolescent-friendly sexually transmitted infection screening and treatment services.

There are high rates of sexually transmitted infections (STIs) worldwide. Adolescents and young adults (AYA) ages 15-24 years remain one of the populations that is most vulnerable to STIs. The goal of this review is to summarize recent international updates in adolescent STI screening and treatment. Normalizing sexual history taking and STI testing, and advocating for adolescents to receive comprehensive sexuality education improves stigma surrounding sexual health. The global rise in syphilis is pervasive and includes high rates of infection among AYA and women of reproductive age - universal screening may be indicated depending on local epidemiology. Gonococcal antimicrobial resistance remains a significant public health concern worldwide, thus judicious use of antimicrobials and reporting cases of resistance is crucial. Sexual health services are increasingly using virtual platforms, which may be an effective strategy for STI testing and treatment among AYA. Specific areas of focus to address the STI epidemic among AYA include reducing stigma surrounding sexual health, screening, and treatment of STIs, especially with the global rise in syphilis and high rates of gonorrhea resistance, in addition to increased use of telehealth services as effective education and intervention strategies.

The use of an imperfect vaccination and awareness campaign in the control of antibiotic resistant gonorrhoea infection: A mathematical modelling perspective

The use of an imperfect vaccination and awareness campaign in the control of antibiotic resistant gonorrhoea infection: A mathematical modelling perspective

Impact of molecular ciprofloxacin resistance testing in management of gonorrhoea in a large urban clinic

ObjectivesAntibiotic resistance in gonorrhoea is of significant public health concern with the emergence of resistance to last-line therapies such as ceftriaxone. Despite around half of Neisseria gonorrhoeae isolates tested in...

Oxydifficidin, a potent Neisseria gonorrhoeae antibiotic due to DedA-assisted uptake and ribosomal protein RplL sensitivity

Gonorrhea, which is caused by Neisseria gonorrhoeae, is the second most reported sexually transmitted infection worldwide. The increasing appearance of isolates that are resistant to approved therapeutics raises the concern that gonorrhea may become untreatable. Here, we serendipitously identified oxydifficidin as a potent N. gonorrhoeae antibiotic through the observation of a Bacillus amyloliquefaciens contaminant in a lawn of N. gonorrhoeae. Oxydifficidin is active against both wild-type and multidrug-resistant N. gonorrhoeae. Its potent activity results from a combination of DedA-assisted uptake into the cytoplasm and the presence of an oxydifficidin-sensitive ribosomal protein L7/L12 (RplL). Our data indicate that oxydifficidin binds to the ribosome at a site that is distinct from other antibiotics and that L7/L12 is uniquely associated with its mode of action. This study opens a potential new avenue for addressing antibiotic resistant gonorrhea and underscores the possibility of identifying overlooked natural products from cultured bacteria, particularly those with activity against previously understudied pathogens.

Target enrichment improves culture-independent detection of Neisseria gonorrhoeae and antimicrobial resistance determinants direct from clinical samples with Nanopore sequencing

Multi-drug-resistant Neisseria gonorrhoeae infection is a significant public health risk. Rapidly detecting N. gonorrhoeae and antimicrobial-resistant (AMR) determinants by metagenomic sequencing of urine is possible, although high levels of host DNA and overgrowth of contaminating species hamper sequencing and limit N. gonorrhoeae genome coverage. We performed Nanopore sequencing of nucleic acid amplification test-positive urine samples and culture-positive urethral swabs with and without probe-based target enrichment, using a custom SureSelect panel, to investigate whether selective enrichment of N. gonorrhoeae DNA improves detection of both species and AMR determinants. Probes were designed to cover the entire N. gonorrhoeae genome, with tenfold enrichment of probes covering selected AMR determinants. Multiplexing was tested in a subset of samples. The proportion of sequence bases classified as N. gonorrhoeae increased in all samples after enrichment, from a median (IQR) of 0.05 % (0.01–0.1 %) to 76 % (42–82 %), giving a corresponding median improvement in fold genome coverage of 365 times (112–720). Over 20-fold coverage, required for robust AMR determinant detection, was achieved in 13/15(87 %) samples, compared to 2/15(13 %) without enrichment. The four samples multiplexed together also achieved >20-fold genome coverage. Coverage of AMR determinants was sufficient to predict resistance conferred by changes in chromosomal genes, where present, and genome coverage also enabled phylogenetic relationships to be reconstructed. Probe-based target enrichment can improve N. gonorrhoeae genome coverage when sequencing DNA extracts directly from urine or urethral swabs, allowing for detection of AMR determinants. Additionally, multiplexing prior to enrichment provided enough genome coverage for AMR detection and reduces the costs associated with this method.

2687. Tetracycline Resistance in Neisseria gonorrhoeae Isolates Among Transgender Women and Men Who Have Sex with Men — eGISP and SURRG, 2018–2021

Abstract Background Doxycycline, a tetracycline analog, is being considered for use as post-exposure prophylaxis (PEP) to reduce bacterial sexually transmitted infections (STIs) among gay, bisexual, and other men who have sex with men (MSM) and transgender women. Pre-existing tetracycline resistance may contribute to the varied effectiveness of doxycycline in preventing Neisseria gonorrhoeae (GC). We examined trends in tetracycline resistance (TetR) and tetM plasmid-mediated high-level tetracycline resistance (TetHLR) among GC isolates collected from MSM and transgender women through national sentinel surveillance. Methods Genital (urethral, urine, vaginal or endocervical), pharyngeal and rectal GC isolates were collected from MSM and transgender women during 2018–2021 at 12 Enhanced Gonococcal Isolate Surveillance Project (eGISP) and 8 Strengthening the U.S. Response to Resistant Gonorrhea (SURRG) sites. We determined overall prevalence of TetR and TetHLR (minimum inhibitory concentration, MIC ≥2 µg/mL and MIC ≥16 µg/mL, respectively) among MSM and transgender women by anatomic site of infection and described annual trends among MSM. Results Among 10,853 isolates collected from 8,667 MSM, overall TetR prevalence was 31% (genital: 31%, pharyngeal: 32%, rectal: 29%), and annual TetR prevalence decreased during 2018–2021 (Table 1). Overall TetHLR prevalence among MSM was 13% (genital: 13%, pharyngeal: 12%, rectal: 12%) and annual TetHLR prevalence for genital and pharyngeal infections increased during 2018–2021. Among 108 isolates collected from 89 transgender women, overall TetR prevalence was 23% (genital: 19%, pharyngeal: 23%, rectal: 25%) and TetHLR prevalence was 9% (genital: 0%, pharyngeal: 10%, rectal: 12%), though numbers were small. Conclusion Approximately 1/3 of GC isolates collected from MSM and 1/4 of GC isolates collected from transgender women were tetracycline resistant. Prevalence of tetracycline resistance was similar across anatomic sites. Providers should continue to follow recommended screening and treatment guidelines for gonorrhea among persons using doxycycline as STI PEP. Additionally, given high levels of TetHLR, enhanced tetracycline resistance surveillance is needed with implementation of doxycycline as STI PEP. Disclosures All Authors: No reported disclosures

Economic evaluation of antimicrobial resistance in curable sexually transmitted infections; a systematic review and a case study.

To provide a summary of the economic and methodological evidence on capturing antimicrobial resistance (AMR) associated costs for curable sexually transmitted infections (STIs). To explore approaches for incorporating the cost of AMR within an economic model evaluating different treatment strategies for gonorrhoea, as a case study. A systematic review protocol was registered on PROSPERO (CRD42022298232). MEDLINE, EMBASE, CINAHL, Cochrane Library, International Health Technology Assessment Database, National Health Service Economic Evaluation Database, and EconLit databases were searched up to August 2022. Included studies were analysed, quality assessed and findings synthesised narratively. Additionally, an economic evaluation which incorporated AMR was undertaken using a decision tree model and primary data from a randomised clinical trial comparing gentamicin therapy with standard treatment (ceftriaxone). AMR was incorporated into the evaluation using three approaches-integrating the additional costs of treating resistant infections, conducting a threshold analysis, and accounting for the societal cost of resistance for the antibiotic consumed. Twelve studies were included in the systematic review with the majority focussed on AMR in gonorrhoea. The cost of ceftriaxone resistant gonorrhoea and the cost of ceftriaxone sparing strategies were significant and related to the direct medical costs from persistent gonorrhoea infections, sequelae of untreated infections, gonorrhoea attributable-HIV transmission and AMR testing. However, AMR definition, the collection and incorporation of AMR associated costs, and the perspectives adopted were inconsistent or limited. Using the review findings, different approaches were explored for incorporating AMR into an economic evaluation comparing gentamicin to ceftriaxone for gonorrhoea treatment. Although the initial analysis showed that ceftriaxone was the cheaper treatment, gentamicin became cost-neutral if the clinical efficacy of ceftriaxone reduced from 98% to 92%. By incorporating societal costs of antibiotic use, gentamicin became cost-neutral if the cost of ceftriaxone treatment increased from £4.60 to £8.44 per patient. Inclusion of AMR into economic evaluations may substantially influence estimates of cost-effectiveness and affect subsequent treatment recommendations for gonorrhoea and other STIs. However, robust data on the cost of AMR and a standardised approach for conducting economic evaluations for STI treatment which incorporate AMR are lacking, and requires further developmental research.

Emerging threat of antimicrobial resistance in Neisseria gonorrhoeae: pathogenesis, treatment challenges, and potential for vaccine development.

The continuous rise of antimicrobial resistance (AMR) is a serious concern as it endangers the effectiveness of healthcare interventions that rely on antibiotics in the long run. The increasing resistance of Neisseria gonorrhoeae, the bacteria responsible for causing gonorrhea, to commonly used antimicrobial drugs, is a major concern. This has now become a critical global health crisis. In the coming years, there is a risk of a hidden epidemic caused by the emergence of gonococcal AMR. This will worsen the global situation. Infections caused by N. gonorrhoeae were once considered easily treatable. However, over time, they have become increasingly resistant to commonly used therapeutic medications, such as penicillin, ciprofloxacin, and azithromycin. As a result, this pathogen is developing into a true "superbug," which means that ceftriaxone is now the only available option for initial empirical treatment. Effective management strategies are urgently needed to prevent severe consequences, such as infertility and pelvic inflammatory disease, which can result from delayed intervention. This review provides a thorough analysis of the escalating problem of N. gonorrhoeae, including its pathogenesis, current treatment options, the emergence of drug-resistant mechanisms, and the potential for vaccine development. We aim to provide valuable insights for healthcare practitioners, policymakers, and researchers in their efforts to combat N. gonorrhoeae antibiotic resistance by elucidating the multifaceted aspects of this global challenge.

Analysis of the dynamics of &lt;i&gt;Neisseria gonorrhоeaе&lt;/i&gt; resistance to antimicrobial drugs in the Russian Federation for the period 2005–2021

Background. Neisseria gonorrhoeae can rapidly develop resistance to antimicrobial agents due to innate mechanisms for the acquisition of antimicrobial resistance genes. Because of the rapid formation of resistance mechanisms of N. gonorrhoeae to the antimicrobial agents used in gonococcal therapy, the risk of incurable forms of the disease is high. The purpose of the study is to to summarize the results of RU-GASP over a 16-year period and assess the trends of N. gonorrhoeae resistance to antimicrobials used in the regimens of antibiotic therapy of gonococcal infection in Russia. Materials and methods. Study Objective. The study included 5356 isolates of N. gonorrhoeae received from January 2005 to December 2021 in State Scientific Center of Dermatovenerology and Cosmetology, Moscow of the Ministry of Health of Russia under the RU-GASP program from specialized medical organizations of dermatovenerological profile of 37 subjects of the Russian Federation. Primary identification of N. gonorrhoeae was performed using bacterioscopic and bacteriological methods. The cultures identified as N. gonorrhoeae were frozen in a cryogenic medium and transported to SSCDC. Received cultures were verified by biochemical criteria on a VITEK 2 Compact analyzer. For cultures identified as N. gonorrhoeae with less than 99% probability, a time-of-flight ionization mass spectrometer MALDI Microflex (Bruker Daltonics GmbH, Germany) was used for mass spectrometric analysis. Antimicrobial susceptibility testing. Sensitivity testing of N. gonorrhoeae to six antimicrobials penicillin, spectinomycin, ceftriaxone, tetracycline, azithromycin and ciprofloxacin was performed by serial dilution in agar with determination of minimum suppressive concentrations (MSC, mg/L). N. gonorrhoeae sensitivity to antibacterial agents was evaluated according to EUCAST criteria (The European Committee on Antimicrobial Susceptibility Testing, 2022, http://www.eucast.org). Results. The study showed the absence of significant changes in the ratio of sensitive and resistant to the action of antimicrobial drugs strains of N. gonorrhoeae that is a consequence of the effectiveness of the RU-GASP program, which allowed to exclude in time from therapeutic use the drugs for which a high proportion of the identified resistant strains was observed. Conclusion. Analysis of RU-GASP results over a 16-year period confirms the use of third-generation cephalosporins (Ceftriaxone, Cefixime) as the drugs of choice for therapy of gonococcal infection, and the aminocyclic antibiotic spectinomycin as an alternative drug. The continued evolution of the molecular mechanisms of antibiotic resistance of N. gonorrhoeae dictates the need to continue the RU-GASP program.

Prevalence, Antibiotic Resistance and Associated Factors of Neisseria gonorrhoeae Among Patients Attending Non-Profitable Private Clinics in Mekelle, Tigrai, Ethiopia.

Globally, Neisseria gonorrhoeae is the second most common cause of bacterial sexually transmitted diseases. The prominent predicament of this bacterium is its complications, non-susceptibility for many drugs, and aggravated transmission of other sexually transmitted infections. There is limited information about the prevalence, antibiotic resistance, and risk factors of N. gonorrhoeae in Tigrai, Ethiopia. Therefore, we aimed to determine the prevalence, antibiotic resistance, and risk factors of N. gonorrhoeae among patients attending non-profitable private clinics in Mekelle, Tigrai, Ethiopia. A cross-sectional study among 229 patients was conducted from February to June 2018. The socio-demographic data and associated factors were gathered using structured questionnaire, and swabs were taken from urethra and cervix of males and females, respectively. Specimens were inoculated on standard bacteriological culture media and antibiotic susceptibility testing was performed using Kirby-Bauer disc diffusion technique following the Clinical and Laboratory Standard Institute. Data were analyzed using Statistical Package for Social Sciences Version 21. The level of significance at p-value <0.05 was considered statistically significant. The overall prevalence of N. gonorrhoeae was 23 (10.04%). High prevalence rates of N. gonorrhoeae were observed in females, urban residents and married ones. N. gonorrhoeae had shown statistically significant association with HIV positive, previous history of STIs, shisha users, Khat (Catha edulis) users, condom non-users and having more than two sexual partners. All isolates showed resistance to penicillin followed by tetracycline 16 (69.6%) and ciprofloxacin 8 (34.8%). Four isolates (7.4%) exhibited resistance to azithromycin with no resistance to ceftriaxone. Twelve (52.2%) isolates showed multidrug resistance (MDR). The prevalence of N. gonorrhoeae and drug resistance, including multidrug resistance, was high in the study. Multiple factors were associated with the acquisition of N. gonorrhoeae. Therefore, behavioral change and communication should be strengthened.

A Genomic Perspective on the Near-term Impact of Doxycycline Post-exposure Prophylaxis on Neisseria gonorrhoeae Antimicrobial Resistance.

Pre-existing tetracycline resistance in Neisseria gonorrhoeae limits the effectiveness of post-exposure prophylaxis (PEP) with doxycycline against gonorrhea, and selection for tetracycline resistance may influence prevalence of multi-drug resistant strains. Using genomic and antimicrobial susceptibility data from N. gonorrhoeae, we assessed the near-term impact of doxycycline PEP on N. gonorrhoeae resistance.